At early stages of heart development, the first and second heart fields are a continuum of lateral head mesoderm-derived, cardiogenic cells.

Pioneering work in the chicken established that the initial development of the heart consists of two stages: the quick assembly of a beating heart, followed by the recruitment of cells from adjacent tissues to deliver the mature in-and outflow tract. Cells to build the primitive heart were dubbed the first heart field (FHF) cells, cells to be recruited later the second heart field (SHF) cells. The current view is that these cells represent distinct, maybe even pre-determined lineages.

Naturally occurring, rostrally conjoining chicken twins attempt to make a forebrain.

Conjoined twinning is a special case of monozygotic, monoamniotic twinning. Human conjoined twinning, and vertebrate conjoined twinning in general, is a very rare phenomenon. It has been suggested that the risk of conjoined twinning increases with some medication and upon assisted reproduction.

Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia.

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.

Simulation of Antral Conditions for Estimating Drug Apparent Equilibrium Solubility after a High-Calorie, High-Fat Meal.

The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate.

The predictive power of baseline metabolic and volumetric [F]FDG PET parameters with different thresholds for early therapy failure and mortality risk in DLBCL patients undergoing CAR-T-cell therapy.

Objective: [F]FDG imaging is an integral part of patient management in CAR-T-cell therapy for recurrent or therapy-refractory DLBCL. The calculation methods of predictive power of specific imaging parameters still remains elusive. With this retrospective study, we sought to evaluate the predictive power of the baseline metabolic parameters and tumor burden calculated with automated segmentation via different thresholding methods for early therapy failure and mortality risk in DLBCL patients.

Outcomes in patients with acute myeloid leukemia older than 70 years within the last 30 years, a single center experience.

As median age of patients with acute myeloid leukemia is 72 years, older patients continue to be a vulnerable cohort representing significant challenges in clinical practice. Patient-specific comorbidities as well as leukemia-specific unfavorable molecular- and cytogenetics confer even poorer outcomes. Treatment of AML therefore needs to be less toxic to prevent harm while lowering or eradicating leukemic burden to prolong survival.

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

Context-Dependent Estrogenic Actions of (+)-Pisatin Produced in Elicited Green or Snow Pea ().

Legumes are a predominant source of isoflavones, termed phytoestrogens, that mimic 17β-estradiol (E2). Phytoalexins are inducible isoflavones produced in plants subjected to environmental stressors (e.g.

Semaphorin 3A repulsion directs the caudal projection of pioneer longitudinal axons in the developing chicken brain.

The medial longitudinal fasciculus (MLF) is the first axon tract to develop in the ventral vertebrate brain. It originates in the diencephalon and projects caudally into the spinal cord, pioneering the path for later developing axons. Previous anatomical and expression analyses in the chicken suggested Semaphorin 3 A (Sema3A) as the candidate to repel the amniote MLF from the forebrain.

Aggressive Lymphoma after CD19 CAR T-Cell Therapy.

The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic and mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant.

Successful generation of fully human, second generation, anti-CD19 CAR T cells for clinical use in patients with diverse autoimmune disorders.

Background: B-cell targeting chimeric antigen receptor (CAR) T-cell therapies, which lead to profound B-cell depletion, have been well-established in hematology-oncology. This deep B-cell depletion mechanism has prompted the exploration of their use in B-cell driven autoimmune diseases. We herein report on the manufacturing of KYV-101, a fully human anti-CD19 CAR T-cell therapy, derived from patients who were treated across a spectrum of autoimmune diseases.

Treatment of trunk defects using perforator flaps: A case series introducing suprascapular artery perforator flap.

This case series explores the efficacy of freestyle perforator flaps, including the newly introduced suprascapular artery perforator flap (SSAP), in reconstructing trunk defects. Over a five-year period, 24 perforator flap procedures were performed on 19 patients, primarily for defect reconstruction after skin tumor and ulcer resections. Flap design was customized using preoperative doppler ultrasound and they were then transferred to defects in a V-Y or propeller fashion.

Drug-Induced Differential Gene Expression Analysis on Nanoliter Droplet Microarrays: Enabling Tool for Functional Precision Oncology.

Drug-induced differential gene expression analysis (DGEA) is essential for uncovering the molecular basis of cell phenotypic changes and understanding individual tumor responses to anticancer drugs. Performing high throughput DGEA is challenging due to the high cost and labor-intensive multi-step sample preparation protocols. In particular, performing drug-induced DGEA on cancer cells derived from patient biopsies is even more challenging due to the scarcity of available cells.

Obesity and leptin in breast cancer angiogenesis.

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer.

Multiplexed Immunophenotyping of Lymphoma Tissue Samples.

High-plex imaging techniques enable the detection and quantification of a multitude of markers in tissue biopsies at single-cell or near-single-cell resolution. In lymphoma, this can facilitate the detection and characterization of cellular phenotypes and interactions, describing both tumor and microenvironmental cells. In combination with other techniques, high-plex imaging allows the investigation of biological mechanisms and clinically relevant biomarkers.

MIAMI-AD (Methylation in Aging and Methylation in AD): an integrative knowledgebase that facilitates explorations of DNA methylation across sex, aging, and Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder with a significant impact on aging populations. DNA methylation (DNAm) alterations have been implicated in both the aging processes and the development of AD. Given that AD affects more women than men, it is also important to explore DNAm changes that occur specifically in each sex.

MOTHER-DB: A Database for Sharing Nonhuman Ovarian Histology Images.

The goal of the Multispecies Ovary Tissue Histology Electronic Repository (MOTHER) project is to establish a collection of nonhuman ovary histology images for multiple species as a resource for researchers and educators. An important component of sharing scientific data is the inclusion of the contextual metadata that describes the data. MOTHER extends the Ecological Metadata Language (EML) for documenting research data, leveraging its data provenance and usage license with the inclusion of metadata for ovary histology images.

A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases.

Purpose: Brain metastases represent the most common intracranial tumors in adults and are associated with a poor prognosis. We used a personalized in vitro drug screening approach to characterize individual therapeutic vulnerabilities in brain metastases.

Methods: Short-term cultures of cancer cells isolated from brain metastasis patients were molecularly characterized using next-generation sequencing and functionally evaluated using high-throughput in vitro drug screening to characterize pharmacological treatment sensitivities.

Overview of the Multispecies Ovary Tissue Histology Electronic Repository†.

The Multispecies Ovary Tissue Histology Electronic Repository (MOTHER) is a publicly accessible repository of ovary histology images. MOTHER includes hundreds of images from nonhuman primates, as well as ovary histology images from an expanding range of other species. Along with an image, MOTHER provides metadata about the image, and for selected species, follicle identification annotations.

Overlapping Stromal Alterations in Myeloid and Lymphoid Neoplasms.

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms.

Nanoalignment by critical Casimir torques.

The manipulation of microscopic objects requires precise and controllable forces and torques. Recent advances have led to the use of critical Casimir forces as a powerful tool, which can be finely tuned through the temperature of the environment and the chemical properties of the involved objects. For example, these forces have been used to self-organize ensembles of particles and to counteract stiction caused by Casimir-Liftshitz forces.